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Zynlonta gets squeezed

ADC Therapeutics’ Zynlonta, an anti-CD19 antibody-drug conjugate, was approved nearly three years ago, and in 2023 generated sales of just $69m. That’s not a great endorsement for a drug that uses a modality at the forefront of current oncology strategies, and now ADC has another small worry: Lotis-5, the phase 3 trial designed to confirm that accelerated approval, has experienced high rates of censoring, it was revealed today, meaning that more than the planned 350 patients might be needed to maintain powering. One problem is that the setting in question, second-line or later diffuse large B-cell lymphoma, is changing fast, with CD19-directed Car-T therapy expanding from relapsed/refractory to second-line use, and anti-CD20 T-cell engagers taking a slice of the late-line pie. Not only did ADC pick a highly competitive target in CD19, Zynlonta uses a tesirine payload (also used in AbbVie’s doomed Rova-T) rather than topo1 inhibition, the current industry favourite, and numerous Zynlonta study discontinuations show how ADC has had to chop and change plans. Zynlonta always looked like a marginal product, and though it seems likely to remain on the market it’s now being squeezed hard by competitors.

 

Selected trials of Zynlonta

StudySettingStatus
Lotis-2Basis for Apr 2021 US accelerated approval for 2L+ DLBCL48% ORR
Lotis-5Confirmatory trial, Rituxan combo vs Rituxan-GemOx in 2L+ DLBCLPFS primary endpoint, enrolment due to complete 2024 after likely expansion
Lotis-7Ph1, various combos in 2L+ DLBCL & 3L+ mixed histologiesData due 2024
Lotis-3Ph1/2 Imbruvica combo in mantle cell lymphomaDiscontinued Mar 2022 to focus on 2L use
Lotis-6Ph2 r/r follicular lymphoma, vs ZydeligDiscontinued after Zydelig withdrawal
Lotis-8Ph1 Rituxan-chop combo in 1L DLBCLDiscontinued Mar 2022 to focus on Lotis-9
Lotis-9Ph2 Rituxan combo in 1L unfit/frail DLBCLDiscontinued Jul 2023

Source: OncologyPipeline.

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